Protective effects of AS-IV on diabetic cardiomyopathy by improving myocardial lipid metabolism in rat models of T2DM

Abstract

Diabetic cardiomyopathy (DCM) is one of the main complications of type 2 diabetes mellitus (T2DM), and it is also one of the main causes of heart failure and death in advanced diabetes. The myocardial lipotoxic injury induced by abnormal lipid metabolism plays an important role in the occurrence and development of DCM, such as myocardial inflammation and fibrosis, ultimately leading to myocardial remodeling and cardiac insufficiency. Astragaloside IV (AS-IV) has many pharmacological effects such as anti-oxidation, anti-inflammatory, immune regulation, and anti-ischemic brain damage. This study was performed to investigate whether AS-IV could prevent T2DM-induced cardiomyopathy and regulate the abnormal myocardial lipid metabolism in diabetes. In this study, the T2DM model was induced by feeding with high-fat food and injected with low-dose STZ in rats. Then the model rats were treated with AS-IV and metformin (Met) for 8 weeks. The results showed that AS-IV improved cardiac systolic and diastolic function, and ameliorated the cardiac histopathological changes in the T2DM rats. Moreover, AS-IV significantly improved circulating TC, TG and HDL levels and cardiac lipid accumulation in T2DM rats as well as in high-fat diet (HFD) rats. Furthermore, AS-IV significantly inhibited the expressions of TNF-α, IL-6 and IL-1β and myocardial fibrosis in T2DM rats, which might be attributed to the improvement of myocardial lipid metabolism, ultimately improving cardiac function in T2DM rats. Taken together, these data suggested that AS-IV has protective effects on T2DM-induced myocardial injury in rats, and its mechanism may be related to the improvement of lipid metabolism in cardiomyocytes.

Keywords: Astragaloside IV; Diabetic cardiomyopathy; Lipid metabolism of cardiomyocytes; Lipid toxicity damage.